Fluorescence and electron microscopic studies of the early development of the substantia nigra and area ventralis tegmenti in the fetal rabbit

Abstract
The anlage of the substantia nigra compacta and the area ventralis tegmenti appears as a fluorescent zone in the midventral proliferation in the caudal mesencephalon of the rabbit at day 14 of gestation. Fluorescence is present in cell bodies and their processes in the mantle layer of the basal plate just ventral to the ependymal zone. By day 16 of gestation, the number of fluorescent cells and processes has increased, and they form an inverted “V” shaped zone in the midline mantle layer. A fluorescent fiber tract, the presumptive mesolimbic and nigroneostriatal pathway, extends from the fluorescent zone through the lateral hypothalamus as far as the caudal portion of the telencephalon. Electron microscopic studies of the inverted “V” shaped anlage show that most of the cells are spindle‐shaped bipolar neuroblasts, but some globular neuroblasts are present as well. The large 800 to 1000 Å dense core vesicle is found in the perikarya of the neuroblasts and also in processes in the neuropil. Axonal growth cones are common, but synaptic profiles are rare. By day 18 of gestation, some of the fluorescent cell bodies have migrated lateral to midline and as far rostral as the central portion of the midbrain. Fluorescent axons of the presumptive nigroneostriatal pathway have reached the putamen and have formed minute varicose terminals. These axons, therefore, have reached their terminal nucleus before their cell bodies have finished migrating to their final positions. Electron microscopic study of the anlage located lateral to midline shows that the cells are multipolar and exhibit extensive new growth of dendrites. Immature synaptic profiles and a few mature junctions are occasionally found in the neuropil. By day 20 of gestation, a distinct substantia nigra compacta and reticulata can be recognized lateral to the area ventralis tegmenti. The neurons of the substantia nigra have relatively abundant perikaryal cytoplasm and the cells are frequently adjacent to one another. The perikarya of the area ventralis are some what smaller and they are spaced more widely apart. Large dense core vesicles are present in some perikarya of both regions. Synaptic terminals are more common, but still not numerous. The meso‐limbic and nigroneostriatal pathway are well established at this stage.